Pembrolizumab + AR Inhibitors for Prostate Cancer
Trial Summary
What is the purpose of this trial?
This is a phase I/II study investigating the combination of 225Ac-J591 (a drug that can deliver radiation to prostate cancer cells) with pembrolizumab (immunotherapy, a drug that increases the immune system's ability to destroy cancer cells). This study will assess whether 225Ac-J591 + pembrolizumab + androgen receptor pathway inhibitor (ARPI) is more effective against prostate cancer than pembrolizumab + ARPI alone.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must continue primary androgen deprivation therapy if you haven't had an orchiectomy, and you can stay on bisphosphonates or denosumab if you've been on a stable dose for at least 4 weeks before starting the trial.
What data supports the effectiveness of the treatment Pembrolizumab + AR Inhibitors for Prostate Cancer?
Research shows that PSMA-targeted therapies, like 225Ac-J591, have been effective in treating prostate cancer by targeting a specific protein highly expressed in these cancer cells. Additionally, androgen receptor inhibitors, such as darolutamide, have shown success in treating prostate cancer by blocking hormones that fuel cancer growth.12345
Is the combination of Pembrolizumab and AR inhibitors safe for prostate cancer treatment?
The safety of 225Ac-J591, a component of the treatment, was evaluated in a study for prostate cancer, showing it was generally well-tolerated with a defined maximum tolerated dose. Another study on 225Ac-L1, a similar compound, showed some off-target effects mainly in the kidneys and liver, but it was considered promising for further evaluation. These findings suggest that while there are some risks, the treatment has been generally safe in studies.12678
How is the treatment with Pembrolizumab and AR Inhibitors for prostate cancer different from other treatments?
This treatment is unique because it combines Pembrolizumab, an immune therapy, with androgen receptor inhibitors and a targeted alpha therapy using 225Ac-J591, which delivers radiation directly to prostate cancer cells. This approach targets prostate-specific membrane antigen (PSMA) on cancer cells, potentially offering a more effective treatment for patients who have developed resistance to standard therapies.124910
Research Team
Scott Tagawa, MD, MS
Principal Investigator
Weill Medical College of Cornell University
Eligibility Criteria
Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has progressed after certain treatments. They must have a good performance status, normal organ function, and agree to contraception during the trial plus 4 months after. Exclusions include other cancers within 2 years, active infections like HIV or hepatitis, recent blood clots or radiotherapy, autoimmune diseases requiring treatment in the last 2 years, current participation in another study drug trial.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment Phase I
Participants receive pembrolizumab, ARPI, and a single dose of 225Ac-J591 to determine the optimal dose
Safety Follow-up
Safety follow-up to monitor dose-limiting toxicity and determine optimal dose for phase II
Treatment Phase II
Randomized treatment with pembrolizumab and ARPI, with or without 225Ac-J591
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- 225Ac-J591
- Androgen receptor pathway inhibitor
- Pembrolizumab
Find a Clinic Near You
Who Is Running the Clinical Trial?
Weill Medical College of Cornell University
Lead Sponsor
Merck Sharp & Dohme LLC
Industry Sponsor
Chirfi Guindo
Merck Sharp & Dohme LLC
Chief Marketing Officer since 2022
Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme LLC
Chief Executive Officer since 2021
JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University
United States Department of Defense
Collaborator